Sickle cell disease (SCD) is an inherited disease characterized by chronic hemolytic anemia with acute and chronic complications. The painful episode that results from tissue ischemia due to vaso-occlusion is the most common reason for admission in children with SCD. Painful vaso-occlusive episodes (VOE) account for a significant number of emergency department and hospital admissions. Morphine via patient controlled analgesia is widely used in hospital settings to manage severe pain in SCD. However, the opioid dose required to achieve pain relief varies considerably within each painful episode, from one episode to another, and between individual patients, and some patients do not receive adequate relief. Our hypothesis is that children with sickle cell disease do not achieve plasma concentrations of morphine at therapeutic levels. We propose to examine whether the lack of response to morphine is related to subtherapeutic morphine concentrations or other factors. Pharmacokinetic parameters of morphine will be compared with known population values during acute painful states. One of the blood samples will be used for genotyping genes (UGT2B7, MOR1, COMT) that may affect response to morphine. Response to morphine will be assessed using pain intensity and pain relief scores, pain location and pain quality, and side effects such as sedation/drowsiness, nausea, itching, hypoventilation (oxygen saturation, respiratory rate), or hypotension (blood pressure). Data from this career development award K23 will be used to design optimal pain management strategies and clinical protocols that aim to minimize the short and long term consequences resulting from untreated or inadequately managed pain during acute vaso-occlusive episodes in children with sickle cell disease. These advancements in pain management will lead Dr. Jacob to her long term career goal as an independent clinical researcher.